RODRIGO OLIVA PEREZ

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  • article 41 Citação(ões) na Scopus
    Consolidation chemotherapy during neoadjuvant chemoradiation (CRT) for distal rectal cancer leads to sustained decrease in tumor metabolism when compared to standard CRT regimen
    (2016) HABR-GAMA, Angelita; PEREZ, Rodrigo O.; JULIAO, Guilherme P. Sao; PROSCURSHIM, Igor; FERNANDEZ, Laura M.; FIGUEIREDO, Marleny N.; GAMA-RODRIGUES, Joaquim; BUCHPIGUEL, Carlos A.
    Background: Neoadjuvant CRT may lead to significant tumor regression in patients with rectal cancer. Different CRT regimens with consolidation chemotherapy may lead to increased rates of complete tumor regression. The purpose of this study was to understand tumor metabolic activity following two different neoadjuvant CRT regimens using sequential PET/CT imaging in two different intervals following RT. Methods: Patients with cT2-4 N0-2 M0 rectal cancer treated by standard CRT (54Gy and 2 cycles of 5FU-based chemotherapy) or extended CRT (54Gy and 6 cycles of 5FU-based chemotherapy) underwent sequential PET/CT imaging at baseline, 6 weeks and 12 weeks from radiation completion. Results: 99 patients undergoing standard CRT were compared to 12 patients undergoing CRT with consolidation chemotherapy. Patients treated with consolidation CRT had increased rates of complete clinical or pathological response (66 % vs. 23 %; p < 0.001). SUVmax variation between baseline and 6 weeks (88 % vs. 63 %; p < 0.001) and between baseline and 12 weeks (90 % vs. 57 %; p < 0.001) were significantly more pronounced among patients undergoing extended CRT with consolidation chemotherapy. An increase in SUVmax between 6 and 12 weeks was observed in 51 % of patients undergoing standard and 18 % of patients undergoing consolidation CRT (p = 0.04). Conclusions: Most of the reduction in tumor metabolism after neoadjuvant CRT occurs within the first 6 weeks from RT completion. In patients undergoing CRT with consolidation chemotherapy, tumors are less likely to regain metabolic activity between 6 and 12 weeks. Therefore, assessment of tumor response may be safely postponed to 12 weeks in patients undergoing extended CRT with consolidation chemotherapy.
  • article 26 Citação(ões) na Scopus
    Extralevator Abdominal Perineal Excision Versus Standard Abdominal Perineal Excision: Impact on Quality of the Resected Specimen and Postoperative Morbidity
    (2017) HABR-GAMA, Angelita; JULIO, Guilherme P. Sao; MATTACHEO, Adrian; CAMPOS-LOBATO, Luiz Felipe de; ALEMAN, Edgar; VAILATI, Bruna B.; GAMA-RODRIGUES, Joaquim; PEREZ, Rodrigo Oliva
    Background Abdominal perineal excision (APE) has been associated with a high risk of positive circumferential resection margin (CRM+) and local recurrence rates in the treatment of rectal cancer. An alternative extralevator approach (ELAPE) has been suggested to improve the quality of resection by avoiding coning of the specimen decreasing the risk of tumor perforation and CRM+. The aim of this study is to compare the quality of the resected specimen and postoperative complication rates between ELAPE and ""standard"" APE. Methods All patients between 1998 and 2014 undergoing abdominal perineal excision for primary or recurrent rectal cancer at a single Institution were reviewed. Between 1998 and 2008, all patients underwent standard APE. In 2009 ELAPE was introduced at our Institution and all patients requiring APE underwent this alternative procedure (ELAPE). The groups were compared according to pathological characteristics, specimen quality (CRM status, perforation and failure to provide the rectum and anus in a single specimen-fragmentation) and postoperative morbidity. Results Fifty patients underwent standard APEs, while 22 underwent ELAPE. There were no differences in CRM+ (10.6 vs. 13.6%; p = 0.70) or tumor perforation rates (8 vs. 0%; p = 0.30) between APE and ELAPE. However, ELAPE were less likely to result in a fragmented specimen (42 vs. 4%; p = 0.002). Advanced pT-stage was also a risk factor for specimen fragmentation (p = 0.03). There were no differences in severe (Grade 3/4) postoperative morbidity (13 vs. 10%; p = 0.5). Perineal wound dehiscences were less frequent among ELAPE (52 vs 13%; p < 0.01). Despite short follow-up (median 21 mo.), 2-year local recurrence-free survival was better for patients undergoing ELAPE when compared to APE (87 vs. 49%; p = 0.04). Conclusions ELAPE may be safely implemented into routine clinical practice with no increase in postoperative morbidity and considerable improvements in the quality of the resected specimen of patients with low rectal cancers.
  • article 63 Citação(ões) na Scopus
    Baseline T Classification Predicts Early Tumor Regrowth After Nonoperative Management in Distal Rectal Cancer After Extended Neoadjuvant Chemoradiation and Initial Complete Clinical Response
    (2017) HABR-GAMA, Angelita; JULIAO, Guilherme Pagin Sao; GAMA-RODRIGUES, Joaquim; VAILATI, Bruna Borba; ORTEGA, Cinthia; FERNANDEZ, Laura Melina; ARAUJO, Sergio Eduardo Alonso; PEREZ, Rodrigo Oliva
    BACKGROUND: Selected patients with rectal cancer and complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively with acceptable outcomes. However, approximate to 20% of these patients will develop early tumor regrowth. Identification of these patients could select candidates for more intensive follow-up. OBJECTIVE: The purpose of this study was to investigate the influence of baseline radiological T classification on recurrences after a complete clinical response managed nonoperatively after chemoradiation. DESIGN: This was a retrospective review of a prospective collected database. SETTINGS: The study was conducted at a single center. PATIENTS: Patients with distal rectal cancer (cT2-4N0-2M0) undergoing extended chemoradiation (54 Gy + 5-fluorouracil-based chemotherapy) were eligible. Patients were reassessed for tumor response at 10 weeks after radiation completion. Patients with complete clinical response (clinical, radiological, and endoscopic) were managed nonoperatively and strictly followed. MAIN OUTCOMES MEASURES: Complete clinical response rates, early tumor regrowth rates (<12 mo), local recurrence-free survival, and distant metastases-free survival were measured. RESULTS: A total of 91 consecutive patients with rectal cancer underwent extended chemoradiation. Sixty-one patients developed initial complete clinical response (67%). cT2 patients developed similar initial complete clinical response rates compared with cT3/T4 (72% vs 63%; p = 0.403). Early tumor regrowths were more frequent among baseline cT3/4 when compared with cT2 patients (30% vs 3%; p = 0.007). There were no differences in late local recurrences (p = 0.593) or systemic recurrences (p = 0.387). Local recurrence-free survival was significantly better for cT2 patients at 1 year (96% vs 69%; p = 0.009). After Cox regression analysis, baseline T stage was an independent predictor of improved local recurrence-free survival at 1 year (p = 0.03; OR = 0.09 (95% CI, 0.01-0.81)). LIMITATIONS: This study was limited by its small sample size, retrospective nature, and short follow-up. CONCLUSIONS: cT2 patients who develop complete clinical response after extended chemoradiation managed nonoperatively are less likely to develop early tumor regrowths when compared with cT3/4 patients. cT3/4 patients should undergo more intensive follow-up after a complete clinical response to allow for early detection of early regrowths.
  • article 93 Citação(ões) na Scopus
    Achieving a Complete Clinical Response After Neoadjuvant Chemoradiation That Does Not Require Surgical Resection: It May Take Longer Than You Think!
    (2019) HABR-GAMA, Angelita; JULIAO, Guilherme P. Sao; FERNANDEZ, Laura M.; VAILATI, Bruna B.; ANDRADE, Andres; ARAUJO, Sergio E. A.; GAMA-RODRIGUES, Joaquim; PEREZ, Rodrigo O.
    BACKGROUND: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed by organ-preserving strategies and acceptable long-term outcomes. Controversy still exists regarding optimal timing for the assessment of tumor response after neoadjuvant chemoradiation. OBJECTIVE: The purpose of this study was to estimate the time interval for achieving complete clinical response using strict endoscopic and clinical criteria after a single neoadjuvant chemoradiation regimen. DESIGN: This was a retrospective review of consecutive patients managed by 54-Gy and consolidation 5-fluorouracil-based chemotherapy. Assessment of response was performed at 10 weeks after radiation. Patients with suspected complete clinical response were offered watch-and-wait strategy and reassessment every 6 to 8 weeks until achievement of strict criteria of complete clinical response or overt residual cancer. SETTINGS: This study was conducted at a single tertiary care center. PATIENTS: Patients with complete clinical response who underwent a successful watch-and-wait strategy until last follow-up were eligible. Dates of radiation completion and achievement of strict endoscopic and clinical criteria (mucosal whitening, teleangiectasia, and no ulceration or irregularity) were recorded. Patients with incomplete response or with initial complete clinical response followed by local recurrence or regrowth were excluded. MAIN OUTCOMES MEASURES: The distribution of time intervals between completion of radiation and achievement of strict complete clinical response was measured. Patients who achieved early complete clinical response (<= 16 wk) were compared with late complete clinical response (>16 wk). RESULTS: A total of 49 patients achieved complete clinical response and were successfully managed nonoperatively. A median interval of 18.7 weeks was observed for achieving strict complete clinical response. Only 38% of patients achieved complete clinical response between 10 and 16 weeks from radiation completion. Patients with earlier cT status (cT2/T3a) achieved a complete clinical response significantly earlier when compared with those patients with more advanced disease (T3b-d/4; 19 vs 26 wk; p = 0.03). LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSIONS: Assessment at 10 to 16 weeks may detect a minority of patients who achieve complete clinical response without additional recurrence after neoadjuvant chemoradiation. Patients suspected for a complete clinical response should be considered for reassessment beyond 16 weeks before definitive management when considered for a watch and wait strategy. See Video Abstract at http://links.lww.com/DCR/A901.
  • article 54 Citação(ões) na Scopus
    Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence
    (2016) PEREZ, Rodrigo Oliva; HABR-GAMA, Angelita; JULIAO, Guilherme Pagin Sao; PROSCURSHIM, Igor; FERNANDEZ, Laura Melina; AZEVEDO, Rafael Ulysses de; VAILATI, Bruna B.; FERNANDES, Felipe Alexandre; GAMA-RODRIGUES, Joaquim
    Transanal endoscopic microsurgery (TEM) has been considered an alternative for selected patients with rectal cancer following neoadjuvant chemoradiation (CRT). Immediate total mesorectal completion for all patients with unfavorable pathological features would result in unnecessary protectomies in a significant proportion of patients. Instead, salvage total mesorectal excision (TME) could be restricted for patients developing local recurrence. The aim of the present study is to determine oncological outcomes of salvage resection for local recurrences following CRT and TEM. Consecutive patients undergoing TEM following neoadjuvant CRT for rectal cancer were reviewed. Patients with ""near"" complete response to CRT (a parts per thousand currency sign3 cm; ycT1-2N0) were offered TEM. Salvage surgery was attempted in the event of a local recurrence. A total of 53 patients were managed by CRT followed by TEM. Unfavorable pathological features were present in 36 patients (68 %). None of the patients underwent immediate completion TME. There were 12 patients who developed local recurrence resulting in a 2-year local recurrence-free survival of 77 % (95 % CI, 53-100 %). Of these patients, 9 developed exclusively local recurrences, and all had at least 1 unfavorable pathological feature in the specimen after TEM (100 %). Eight patients (8 of 9) underwent salvage resection (abdominoperineal resection [APR] in 87 %) with CRM+ in 7 of 8 patients (87 %). Four patients developed local re-recurrence after a median 36 months of follow-up. The 2-year local re-recurrence free survival was 60 %. Salvage resection for local recurrence following CRT and TEM is associated with high rates of R1 resection (CRM+) and local re-recurrence. Immediate completion of TME should be considered for patients with unfavorable pathological features after TEM.
  • article 98 Citação(ões) na Scopus
    Impact of Organ-Preserving Strategies on Anorectal Function in Patients with Distal Rectal Cancer Following Neoadjuvant Chemoradiation
    (2016) HABR-GAMA, Angelita; LYNN, Patricio B.; JORGE, J. Marcio N.; JULIAO, Guilherme P. Sao; PROSCURSHIM, Igor; GAMA-RODRIGUES, Joaquim; FERNANDEZ, Laura M.; PEREZ, Rodrigo O.
    BACKGROUND: Organ-preserving strategies have been considered for patients with distal rectal cancer and complete or near-complete response to neoadjuvant chemoradiation to avoid the functional consequences of radical surgery. Transanal endoscopic microsurgery and no immediate surgery (watch and wait) have been considered in selected patients. OBJECTIVE: The aim of this study is to compare anorectal function following these 2 organ-preserving strategies (transanal endoscopic microsurgery and watch and wait) for rectal cancer with complete or near-complete response to neoadjuvant chemoradiation. DESIGN: This study is based on the comparison of prospectively collected data. SETTINGS: This study was conducted at a single center. PATIENTS: Consecutive patients with distal rectal cancer undergoing neoadjuvant chemoradiation (50.4-54 Gy and 5-fluorouracil-based chemotherapy) were prospectively studied. Patients with complete clinical response were managed by watch and wait. Patients with near-complete response (<= 3 cm, ycT1-2N0) were managed by transanal endoscopic microsurgery. MAIN OUTCOME MEASURES: Functional outcomes were determined by anorectal manometry and Fecal Incontinence Index and Quality of Life assessment. RESULTS: Two groups of patients were included in the study. Twenty-nine patients with near-complete response undergoing transanal endoscopic microsurgery and 53 with complete response after watch and wait were assessed. Baseline features were similar between groups. Patients undergoing transanal endoscopic microsurgery had worse resting/squeeze pressures (p = 0.004) and rectal capacity (p = 0.002). In addition, their incontinence scores (2.3 vs 6.5; p < 0.001) and quality-of-life questionnaire responses (in all domains; p <= 0.01) were significantly worse in comparison with patients undergoing watch and wait. LIMITATIONS: This study was limited by the small sample size and the absence of baseline anorectal function information. CONCLUSIONS: Nonoperative management of patients with complete clinical response following chemoradiation results in better anorectal function in comparison with patients with near-complete response managed by transanal endoscopic microsurgery. In the absence of clinically detectable residual cancer, this latter approach may result in significant worsening of anorectal function.
  • article 52 Citação(ões) na Scopus
    Intratumoral Genetic Heterogeneity in Rectal Cancer Are Single Biopsies representative of the entirety of the tumor?
    (2017) BETTONI, Fabiana; MASOTTI, Cibele; HABR-GAMA, Angelita; CORREA, Bruna R.; GAMA-RODRIGUES, Joaquim; VIANNA, Maria R.; VAILATI, Bruna B.; JULIAO, Guilherme P. Sao; FERNANDEZ, Laura M.; GALANTE, Pedro A.; CAMARGO, Anamaria A.; PEREZ, Rodrigo O.
    Objective: Demonstrate intratumoral genetic heterogeneity in rectal cancer. Background: Several clinical management decisions in rectal cancer may be influenced by pretreatment biopsy information. However, in the setting of significant intratumoral heterogeneity, biopsies may not be representative of the entirety of the tumor and limit the reliability of the information provided from them for clinical decision management. Methods: Three fragments from a single rectal adenocarcinoma were chosen for whole-exome sequencing followed by mutation detection analysis. About 25 Gb of unambiguously mapped sequences were generated for each sample resulting in a median fold-coverage of 35x. Captured sequences mapped to the reference human genome were then used for the detection of somatic point mutations. Results: Overall, 193 unique somatic point mutations were identified. Only 53 (27%) of these were shared by all three fragments, including known genes involved in early phases of the adenoma-carcinoma sequence (such as, APC). Approximately, 115 (59%) mutations were exclusively present in only one of the fragments, including mutations in ""driver"" genes (DNAH12). Jaccard distances showed a median distance of 0.603 for pair-wise comparison of fragments indicating significant heterogeneity between them. Conclusions: Considerable intratumoral heterogeneity is present among naive rectal cancers. The majority of point mutations detected in different fragments from rectal cancers are frequently unique to a single fragment. These findings support that gene mutations found on single pretreatment biopsies will not necessarily be representative of mutations present in the entirety of the tumor and therefore may limit the utility of the biological information provided by single biopsy fragments for clinical management decisions.
  • article 106 Citação(ões) na Scopus
    Role of biopsies in patients with residual rectal cancer following neoadjuvant chemoradiation after downsizing: can they rule out persisting cancer?
    (2012) PEREZ, R. O.; HABR-GAMA, A.; PEREIRA, G. V.; LYNN, P. B.; ALVES, P. A.; PROSCURSHIM, I.; RAWET, V.; GAMA-RODRIGUES, J.
    Aim The study aimed to determine the value of postchemoradiation biopsies, performed after significant tumour downsizing following neoadjuvant therapy, in predicting complete tumour regression in patients with distal rectal cancer. Method A retrospective comparative study was performed in patients with rectal cancer who achieved an incomplete clinical response after neoadjuvant chemoradiotherapy. Patients with significant tumour downsizing (> 30% of the initial tumour size) were compared with controls (< 30% reduction of the initial tumour size). During flexible proctoscopy carried out postchemoradiation, biopsies were performed using 3-mm biopsy forceps. The biopsy results were compared with the histopathological findings of the resected specimen. UICC (Union for International Cancer Control) ypTNM classification, tumour differentiation and regression grade were evaluated. The main outcome measures were sensitivity and specificity, negative and positive predictive values, and accuracy of a simple forceps biopsy for predicting pathological response after neoadjuvant chemoradiotherapy. Results Of the 172 patients, 112 were considered to have had an incomplete clinical response and were included in the study. Thirty-nine patients achieved significant tumour downsizing and underwent postchemoradiation biopsies. Overall, 53 biopsies were carried out. Of the 39 patients who achieved significant tumour downsizing, the biopsy result was positive in 25 and negative in 14. Only three of the patients with a negative biopsy result were found to have had a complete pathological response (giving a negative predictive value of 21%). Considering all biopsies performed, only three of 28 negative biopsies were true negatives, giving a negative predictive value of 11%. Conclusion In patients with distal rectal cancer undergoing neoadjuvant chemoradiation, post-treatment biopsies are of limited clinical value in ruling out persisting cancer. A negative biopsy result after a near-complete clinical response should not be considered sufficient for avoiding a radical resection.
  • article 110 Citação(ões) na Scopus
    Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation Long-Term Results of a Prospective Trial (National Clinical Trial 00254683)
    (2012) PEREZ, Rodrigo Oliva; HABR-GAMA, Angelita; GAMA-RODRIGUES, Joaquim; PROSCURSHIM, Igor; JULIAO, Guilherme Pagin Sao; LYNN, Patricio; ONO, Carla Rachel; CAMPOS, Fabio Guilherme; SOUSA JR., Afonso Henrique Silva e; IMPERIALE, Antonio Rocco; NAHAS, Sergio Carlos; BUCHPIGUEL, Carlos Alberto
    BACKGROUND: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. METHODS: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. RESULTS: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false-positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. CONCLUSIONS: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;35013511. (C) 2011 American Cancer Society.
  • article 11 Citação(ões) na Scopus
    Magnetic resonance imaging following neoadjuvant chemoradiation and transanal endoscopic microsurgery for rectal cancer
    (2017) JULIAO, G. P. Sao; ORTEGA, C. D.; VAILATI, B. B.; HABR-GAMA, A.; FERNANDEZ, L. M.; GAMA-RODRIGUES, J.; ARAUJO, S. E.; PEREZ, R. O.
    Aim Full-thickness local excision after neoadjuvant chemoradiotherapy (CRT) for patients with rectal cancer and incomplete clinical response has been a treatment strategy for organ preservation. Follow-up of these patients is challenging since anatomic distortion and postoperative changes may be clinically indistinguishable from tumour recurrence. MRI may have a role in detecting recurrence. The aim of this study was to describe the MRI findings during follow-up in patients having local excision following CRT with and without local recurrence. Method The data were collected retrospectively from a single centre. Fifty-three patients with rectal cancer who had full-thickness local excision after neoadjuvant CRT and near-complete response were eligible for the study. Patients with local recurrence were treated by radical salvage surgery. The main outcome was local MRI assessment findings during follow-up. Results Fifteen patients (five who developed local recurrence and 10 with no evidence of local recurrence) had MR images available for review and were included in the study. High signal intensity and thickening of the rectal wall were present in all patients with recurrent disease within the rectal wall. Overall, 80% of the patients with recurrence showed diffusion restriction. MRI mesorectal fascia status and circumferential resection margin showed agreement in all cases. A low signal intensity scar was seen in all patients without recurrent disease. Conclusion MRI shows high signal intensity and thickening of the rectal wall in recurrent disease in comparison to a low signal intensity fibrotic scar in non-recurrent disease. These findings may be useful in surveillance of these patients.